CA2657381A1 - Derives de la [4,5']bipyrimidinyl-6,4'-diamine utilises comme inhibiteurs de la proteine kinase - Google Patents

Info

Publication number

CA2657381A1

CA2657381A1 CA002657381A CA2657381A CA2657381A1 CA 2657381 A1 CA2657381 A1 CA 2657381A1 CA 002657381 A CA002657381 A CA 002657381A CA 2657381 A CA2657381 A CA 2657381A CA 2657381 A1 CA2657381 A1 CA 2657381A1

Authority

CA

Canada

Prior art keywords

pyridin

dimethoxy

bipyrimidinyl

phenyl

methyl

Prior art date

2006-07-12

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• BCJLFTCREDMRCK-UHFFFAOYSA-N 6-(4-aminopyrimidin-5-yl)pyrimidin-4-amine Chemical class C1=NC(N)=CC(C=2C(=NC=NC=2)N)=N1 BCJLFTCREDMRCK-UHFFFAOYSA-N 0.000 title description 2
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title description 2
• 239000003909 protein kinase inhibitor Substances 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 222
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 48
• 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 44
• 102000020233 phosphotransferase Human genes 0.000 claims abstract description 44
• 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 claims abstract description 42
• 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 claims abstract description 42
• 230000000694 effects Effects 0.000 claims abstract description 41
• 238000000034 method Methods 0.000 claims abstract description 37
• 201000010099 disease Diseases 0.000 claims abstract description 35
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
• -1 pyrrolidino, piperidino, piperazino Chemical group 0.000 claims description 100
• 229910052739 hydrogen Inorganic materials 0.000 claims description 64
• 239000001257 hydrogen Substances 0.000 claims description 63
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 60
• 239000000203 mixture Substances 0.000 claims description 45
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 43
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 40
• 150000003839 salts Chemical class 0.000 claims description 36
• 125000002950 monocyclic group Chemical group 0.000 claims description 34
• 229910052757 nitrogen Inorganic materials 0.000 claims description 29
• 229920006395 saturated elastomer Polymers 0.000 claims description 21
• 230000005764 inhibitory process Effects 0.000 claims description 20
• 229910052717 sulfur Inorganic materials 0.000 claims description 20
• 150000001204 N-oxides Chemical class 0.000 claims description 16
• 125000002619 bicyclic group Chemical group 0.000 claims description 15
• 229910052799 carbon Inorganic materials 0.000 claims description 14
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 14
• 229910052760 oxygen Inorganic materials 0.000 claims description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
• 125000005843 halogen group Chemical group 0.000 claims description 11
• 239000003814 drug Substances 0.000 claims description 9
• 239000012453 solvate Substances 0.000 claims description 9
• 241001465754 Metazoa Species 0.000 claims description 8
• 150000002431 hydrogen Chemical group 0.000 claims description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
• 230000007170 pathology Effects 0.000 claims description 7
• 108091008598 receptor tyrosine kinases Proteins 0.000 claims description 7
• 102000027426 receptor tyrosine kinases Human genes 0.000 claims description 7
• 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 6
• 208000034578 Multiple myelomas Diseases 0.000 claims description 6
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 6
• 125000003118 aryl group Chemical group 0.000 claims description 6
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 6
• 125000006203 morpholinoethyl group Chemical group [H]C([H])(*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 6
• 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 6
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
• 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 4
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 4
• 206010005003 Bladder cancer Diseases 0.000 claims description 4
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
• 125000001246 bromo group Chemical group Br* 0.000 claims description 4
• 125000001153 fluoro group Chemical group F* 0.000 claims description 4
• DEQWECAWVNDIHY-UHFFFAOYSA-N n-(2,6-dichloro-3,5-dimethoxyphenyl)-3-[6-[[5-(morpholin-4-ylmethyl)pyridin-2-yl]amino]pyrimidin-4-yl]pyrazin-2-amine Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=NC=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCOCC4)=CC=3)C=2)=C1Cl DEQWECAWVNDIHY-UHFFFAOYSA-N 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• 125000001424 substituent group Chemical group 0.000 claims description 4
• 201000005112 urinary bladder cancer Diseases 0.000 claims description 4
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
• 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
• ZXOGVOGAINUMFX-UHFFFAOYSA-N 1-[3-[[6-[4-(2-chloro-6-fluoro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]phenyl]ethanol Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3C=C(C=CC=3)C(C)O)C=2)=C1F ZXOGVOGAINUMFX-UHFFFAOYSA-N 0.000 claims description 2
• NMMBKQUZGJYFKU-UHFFFAOYSA-N 1-[4-[[6-[[6-[4-(2,6-dichloro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]pyridin-3-yl]methyl]piperazin-1-yl]ethanone Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCN(CC4)C(C)=O)=CC=3)C=2)=C1Cl NMMBKQUZGJYFKU-UHFFFAOYSA-N 0.000 claims description 2
• FFHPXSVUVZJSNL-UHFFFAOYSA-N 1-[6-[[6-[3-(2,6-dichloro-3,5-dimethoxyanilino)pyrazin-2-yl]pyrimidin-4-yl]amino]pyridin-3-yl]ethanol Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=NC=CN=2)C=2N=CN=C(NC=3N=CC(=CC=3)C(C)O)C=2)=C1Cl FFHPXSVUVZJSNL-UHFFFAOYSA-N 0.000 claims description 2
• YWENEVBVNPLSKO-UHFFFAOYSA-N 1-[6-[[6-[4-(2,6-difluoro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]pyridin-3-yl]ethanol Chemical compound COC1=CC(OC)=C(F)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(=CC=3)C(C)O)C=2)=C1F YWENEVBVNPLSKO-UHFFFAOYSA-N 0.000 claims description 2
• MMBKQAIUIYITQS-UHFFFAOYSA-N 2,4-dichloro-3-[[5-[6-[[5-[(dimethylamino)methyl]pyridin-2-yl]amino]pyrimidin-4-yl]pyrimidin-4-yl]amino]-n-ethyl-5-methoxybenzamide Chemical compound CCNC(=O)C1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN(C)C)=CC=3)C=2)=C1Cl MMBKQAIUIYITQS-UHFFFAOYSA-N 0.000 claims description 2
• LEUCXSBKOBGVNL-UHFFFAOYSA-N 2,4-dichloro-n-ethoxy-5-methoxy-3-[[5-[6-[[5-(morpholin-4-ylmethyl)pyridin-2-yl]amino]pyrimidin-4-yl]pyrimidin-4-yl]amino]benzamide Chemical compound CCONC(=O)C1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCOCC4)=CC=3)C=2)=C1Cl LEUCXSBKOBGVNL-UHFFFAOYSA-N 0.000 claims description 2
• SXQRVKOMWGPOPD-UHFFFAOYSA-N 2,4-dichloro-n-ethyl-3-[[5-[6-[4-(4-ethylpiperazin-1-yl)anilino]pyrimidin-4-yl]pyrimidin-4-yl]amino]-5-methoxybenzamide Chemical compound CCNC(=O)C1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3C=CC(=CC=3)N3CCN(CC)CC3)C=2)=C1Cl SXQRVKOMWGPOPD-UHFFFAOYSA-N 0.000 claims description 2
• CYUUUFLXAZFEMI-UHFFFAOYSA-N 2,4-dichloro-n-ethyl-5-methoxy-3-[[5-[6-[[4-(morpholin-4-ylmethyl)pyridin-2-yl]amino]pyrimidin-4-yl]pyrimidin-4-yl]amino]benzamide Chemical compound CCNC(=O)C1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC=C(CN4CCOCC4)C=3)C=2)=C1Cl CYUUUFLXAZFEMI-UHFFFAOYSA-N 0.000 claims description 2
• KSNIERJLJHXJRM-UHFFFAOYSA-N 2,4-dichloro-n-ethyl-5-methoxy-3-[[5-[6-[[4-[(4-methylpiperazin-1-yl)methyl]pyridin-2-yl]amino]pyrimidin-4-yl]pyrimidin-4-yl]amino]benzamide Chemical compound CCNC(=O)C1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC=C(CN4CCN(C)CC4)C=3)C=2)=C1Cl KSNIERJLJHXJRM-UHFFFAOYSA-N 0.000 claims description 2
• UXXATKKDZCYSAG-UHFFFAOYSA-N 2,4-dichloro-n-ethyl-5-methoxy-3-[[5-[6-[[5-(morpholin-4-ylmethyl)pyridin-2-yl]amino]pyrimidin-4-yl]pyrimidin-4-yl]amino]benzamide Chemical compound CCNC(=O)C1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCOCC4)=CC=3)C=2)=C1Cl UXXATKKDZCYSAG-UHFFFAOYSA-N 0.000 claims description 2
• QBSIHXNNAGOXGC-UHFFFAOYSA-N 2,4-dichloro-n-ethyl-5-methoxy-3-[[5-[6-[[5-(pyrrolidin-1-ylmethyl)pyridin-2-yl]amino]pyrimidin-4-yl]pyrimidin-4-yl]amino]benzamide Chemical compound CCNC(=O)C1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCCC4)=CC=3)C=2)=C1Cl QBSIHXNNAGOXGC-UHFFFAOYSA-N 0.000 claims description 2
• FJFMBBQFQYKUPE-UHFFFAOYSA-N 2,4-dichloro-n-ethyl-5-methoxy-3-[[5-[6-[[5-[(4-methylpiperazin-1-yl)methyl]pyridin-2-yl]amino]pyrimidin-4-yl]pyrimidin-4-yl]amino]benzamide Chemical compound CCNC(=O)C1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCN(C)CC4)=CC=3)C=2)=C1Cl FJFMBBQFQYKUPE-UHFFFAOYSA-N 0.000 claims description 2
• RMCRWRACPLILML-UHFFFAOYSA-N 2-[4-[6-[[6-[3-(2,6-dichloro-3,5-dimethoxyanilino)pyrazin-2-yl]pyrimidin-4-yl]amino]pyridin-3-yl]piperazin-1-yl]ethanol Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=NC=CN=2)C=2N=CN=C(NC=3N=CC(=CC=3)N3CCN(CCO)CC3)C=2)=C1Cl RMCRWRACPLILML-UHFFFAOYSA-N 0.000 claims description 2
• XUPGEWMUHRNEHO-UHFFFAOYSA-N 2-[4-[[6-[[6-[4-(2-chloro-3,5-dimethoxy-6-methylanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]pyridin-3-yl]methyl]piperazin-1-yl]ethanol Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCN(CCO)CC4)=CC=3)C=2)=C1C XUPGEWMUHRNEHO-UHFFFAOYSA-N 0.000 claims description 2
• XYIBIKYKRKQRGW-UHFFFAOYSA-N 2-[4-[[6-[[6-[4-(2-fluoro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]pyridin-3-yl]methyl]piperazin-1-yl]ethanol Chemical compound COC1=CC(OC)=CC(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCN(CCO)CC4)=CC=3)C=2)=C1F XYIBIKYKRKQRGW-UHFFFAOYSA-N 0.000 claims description 2
• YUCPGZSYMDFVJE-UHFFFAOYSA-N 3-(6-aminopyrimidin-4-yl)-n-(2,6-dichlorophenyl)pyrazin-2-amine Chemical class C1=NC(N)=CC(C=2C(=NC=CN=2)NC=2C(=CC=CC=2Cl)Cl)=N1 YUCPGZSYMDFVJE-UHFFFAOYSA-N 0.000 claims description 2
• CIHFDNJEKWTWLJ-UHFFFAOYSA-N 4-[[6-[[6-[4-(2,6-dichloro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]pyridin-3-yl]methyl]piperazine-1-carboxamide Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCN(CC4)C(N)=O)=CC=3)C=2)=C1Cl CIHFDNJEKWTWLJ-UHFFFAOYSA-N 0.000 claims description 2
• VHTOEAQTTZXCOA-UHFFFAOYSA-N 6-[4-(2-chloro-3,5-dimethoxy-6-methylanilino)pyrimidin-5-yl]-n-[5-(morpholin-4-ylmethyl)pyridin-2-yl]pyrimidin-4-amine Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCOCC4)=CC=3)C=2)=C1C VHTOEAQTTZXCOA-UHFFFAOYSA-N 0.000 claims description 2
• 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
• 201000010881 cervical cancer Diseases 0.000 claims description 2
• IMLBLNTWKDEHCS-UHFFFAOYSA-N n-(2,6-dichloro-3,5-dimethoxyphenyl)-3-[6-[[4-(2-morpholin-4-ylethyl)pyridin-2-yl]amino]pyrimidin-4-yl]pyrazin-2-amine Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=NC=CN=2)C=2N=CN=C(NC=3N=CC=C(CCN4CCOCC4)C=3)C=2)=C1Cl IMLBLNTWKDEHCS-UHFFFAOYSA-N 0.000 claims description 2
• DTGFLQCDFNOWSG-UHFFFAOYSA-N n-(2,6-dichloro-3,5-dimethoxyphenyl)-3-[6-[[4-(morpholin-4-ylmethyl)pyridin-2-yl]amino]pyrimidin-4-yl]pyrazin-2-amine Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=NC=CN=2)C=2N=CN=C(NC=3N=CC=C(CN4CCOCC4)C=3)C=2)=C1Cl DTGFLQCDFNOWSG-UHFFFAOYSA-N 0.000 claims description 2
• XTBHWTYTNGOVJE-UHFFFAOYSA-N n-(2,6-dichlorophenyl)-3-[6-[4-(4-ethylpiperazin-1-yl)anilino]pyrimidin-4-yl]pyrazin-2-amine Chemical class C1CN(CC)CCN1C(C=C1)=CC=C1NC1=CC(C=2C(=NC=CN=2)NC=2C(=CC=CC=2Cl)Cl)=NC=N1 XTBHWTYTNGOVJE-UHFFFAOYSA-N 0.000 claims description 2
• RWKOJOJGEWDVNF-UHFFFAOYSA-N n-(2,6-dichlorophenyl)-3-[6-[[5-(2-morpholin-4-ylethyl)pyridin-2-yl]amino]pyrimidin-4-yl]pyrazin-2-amine Chemical class ClC1=CC=CC(Cl)=C1NC1=NC=CN=C1C1=CC(NC=2N=CC(CCN3CCOCC3)=CC=2)=NC=N1 RWKOJOJGEWDVNF-UHFFFAOYSA-N 0.000 claims description 2
• CQYCMUYFDNMOFE-UHFFFAOYSA-N n-(2,6-dichlorophenyl)-3-[6-[[5-(morpholin-4-ylmethyl)pyridin-2-yl]amino]pyrimidin-4-yl]pyrazin-2-amine Chemical class ClC1=CC=CC(Cl)=C1NC1=NC=CN=C1C1=CC(NC=2N=CC(CN3CCOCC3)=CC=2)=NC=N1 CQYCMUYFDNMOFE-UHFFFAOYSA-N 0.000 claims description 2
• CDQIWPKYEYLVKR-UHFFFAOYSA-N n-(2-chloro-6-fluoro-3,5-dimethoxyphenyl)-3-[6-[[5-(morpholin-4-ylmethyl)pyridin-2-yl]amino]pyrimidin-4-yl]pyrazin-2-amine Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=NC=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCOCC4)=CC=3)C=2)=C1F CDQIWPKYEYLVKR-UHFFFAOYSA-N 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 37
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 8
• WIGBPFMLSVEBSH-UHFFFAOYSA-N 1-[3-[[6-[4-(2,6-difluoro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]phenyl]ethanol Chemical compound COC1=CC(OC)=C(F)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3C=C(C=CC=3)C(C)O)C=2)=C1F WIGBPFMLSVEBSH-UHFFFAOYSA-N 0.000 claims 1
• KDHDEIZNVKDEEH-UHFFFAOYSA-N 1-[4-[6-[[6-[3-(2,6-dichloro-3,5-dimethoxyanilino)pyrazin-2-yl]pyrimidin-4-yl]amino]pyridin-3-yl]piperazin-1-yl]-2-hydroxyethanone Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=NC=CN=2)C=2N=CN=C(NC=3N=CC(=CC=3)N3CCN(CC3)C(=O)CO)C=2)=C1Cl KDHDEIZNVKDEEH-UHFFFAOYSA-N 0.000 claims 1
• PNCFUDLLXJUXSH-UHFFFAOYSA-N 1-[4-[[6-[[6-[4-(2,6-difluoro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]pyridin-3-yl]methyl]piperazin-1-yl]ethanone Chemical compound COC1=CC(OC)=C(F)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCN(CC4)C(C)=O)=CC=3)C=2)=C1F PNCFUDLLXJUXSH-UHFFFAOYSA-N 0.000 claims 1
• GSQTWFXIKOAEQF-UHFFFAOYSA-N 1-[4-[[6-[[6-[4-(2-chloro-6-fluoro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]pyridin-3-yl]methyl]piperazin-1-yl]ethanone Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCN(CC4)C(C)=O)=CC=3)C=2)=C1F GSQTWFXIKOAEQF-UHFFFAOYSA-N 0.000 claims 1
• VOFHZBUHDJQGEE-UHFFFAOYSA-N 1-[6-[4-(2,6-dichloro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]-3-(2-morpholin-4-ylethyl)urea Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC(=O)NCCN3CCOCC3)C=2)=C1Cl VOFHZBUHDJQGEE-UHFFFAOYSA-N 0.000 claims 1
• MMEYHALTWHKHFC-UHFFFAOYSA-N 1-[6-[4-(2,6-dichloro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC(=O)NCCN3CCN(C)CC3)C=2)=C1Cl MMEYHALTWHKHFC-UHFFFAOYSA-N 0.000 claims 1
• WXASKJZNTGILEK-UHFFFAOYSA-N 1-[6-[[6-[4-(2-chloro-6-fluoro-3,5-dimethoxyanilino)pyrimidin-5-yl]pyrimidin-4-yl]amino]pyridin-3-yl]ethanol Chemical compound COC1=CC(OC)=C(Cl)C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(=CC=3)C(C)O)C=2)=C1F WXASKJZNTGILEK-UHFFFAOYSA-N 0.000 claims 1
• NTIGRSQJQQNUJH-UHFFFAOYSA-N 2,4-dichloro-5-methoxy-3-[[5-[6-[[5-(morpholin-4-ylmethyl)pyridin-2-yl]amino]pyrimidin-4-yl]pyrimidin-4-yl]amino]-n-[3-(trifluoromethyl)phenyl]benzamide Chemical compound ClC=1C(NC=2C(=CN=CN=2)C=2N=CN=C(NC=3N=CC(CN4CCOCC4)=CC=3)C=2)=C(Cl)C(OC)=CC=1C(=O)NC1=CC=CC(C(F)(F)F)=C1 NTIGRSQJQQNUJH-UHFFFAOYSA-N 0.000 claims 1
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